1,2-Dichloroethane → HCID 71699282, compound

HRID 518229Notes

Reaction equation

HRID 518229 reaction equation
[C:1]1([CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][C:12]3([NH:19][C:18](=[O:20])[C:17]4[CH:21]=[C:22](/[CH:25]=[CH:26]/[C:27](O)=[O:28])[CH:23]=[CH:24][C:16]=4[O:15]3)[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)C[Cl:32].C1C=CC2[N:42]([OH:43])N=NC=2C=1.NOC1CCCCO1>C(Cl)Cl>[ClH:32].[C:1]1([CH2:7][CH2:8][N:9]2[CH2:10][CH2:11][C:12]3([NH:19][C:27](=[O:28])[C:26]4[CH:25]=[C:22](/[CH:21]=[CH:17]/[C:18]([NH:42][OH:43])=[O:20])[CH:23]=[CH:24][C:16]=4[O:15]3)[CH2:13][CH2:14]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 66932294HCID 66932294, compound

Product 1

HCID 71699282HCID 71699282, compoundYield 64.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(E)-3-{1′-(2-Phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid (240 mg, 0.612 mmol) was dissolved in DCM (20 ml) and TEA (0.17 ml, 1.23 mmol). EDC (169 mg, 0.88 mmol), HOBT (119 mg, 0.88 mmol) and NH2OTHP (86 mg, 0.74 mmol) were added and the mixture was stirred at RT overnight. The mixture was partitioned between DCM and 5% aqueous NaHCO3 and the organic phase was dried over Na2SO4 and evaporated. The crude mixture was purified by column chromatography (eluent: DCM/MeOH 95:5). The resulting (E)-3-{1′-(2-phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide was dissolved in DCM and treated with 4 M HCl in dioxane for 3 h. The precipitate was filtered off and washed with DCM to give (E)-3-{1′-(2-phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-hydroxy-acrylamide hydrochloride (175 mg) as a white solid.

Workup

  1. customThe mixture was partitioned between DCM and 5% aqueous NaHCO3
  2. dry with materialthe organic phase was dried over Na2SO4
  3. customevaporated
  4. customThe crude mixture was purified by column chromatography (eluent: DCM/MeOH 95:5)
  5. dissolutionThe resulting (E)-3-{1′-(2-phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide was dissolved in DCM
  6. additiontreated with 4 M HCl in dioxane for 3 h
  7. filtrationThe precipitate was filtered off
  8. washwashed with DCM

Sources & evidence

ORD record
ord-7a1317b9e23f4a69b58b7448dd06f8a1
Source dataset
uspto-grants-2015_08
Patent number
US09115148B2

Reaction notes

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